title: Efficacy of parainfluenza virus 5 mutants expressing hemagglutinin from H5N1 influenza A virus in mice.
abstract: Parainfluenza virus 5 (PIV5) is a promising viral vector for vaccine development. PIV5 is safe, stable, efficacious, cost-effective to produce and, most interestingly, it overcomes preexisting antivector immunity. We have recently reported that PIV5 expressing the hemagglutinin (HA) from highly pathogenic avian influenza (HPAI) virus H5N1 (PIV5-H5) provides sterilizing immunity against lethal doses of HPAI H5N1 infection in mice. It is thought that induction of apoptosis can lead to enhanced antigen presentation. Previously, we have shown that deleting the SH gene and the conserved C terminus of the V gene in PIV5 results in mutant viruses (PIV5ΔSH and PIV5VΔC) that enhance induction of apoptosis. In this study, we inserted the HA gene of H5N1 into PIV5ΔSH (PIV5ΔSH-H5) or PIV5VΔC (PIV5VΔC-H5) and compared their efficacies as vaccine candidates to PIV5-H5. We have found that PIV5ΔSH-H5 induced the highest levels of anti-HA antibodies, the strongest T cell responses, and the best protection against an H5N1 lethal challenge in mice. These results suggest that PIV5ΔSH is a better vaccine vector than wild-type PIV5.
authors.affiliation: Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia, USA.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Li
authors.forename: Jon D
authors.initials: JD
authors.lastname: Gabbard
authors.forename: Alaina
authors.initials: A
authors.lastname: Mooney
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Chen
authors.forename: S Mark
authors.initials: SM
authors.lastname: Tompkins
authors.forename: Biao
authors.initials: B
authors.lastname: He
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D017951:Antigen Presentation; D017209:Apoptosis; D002522:Chlorocebus aethiops; D005260:Female; D005814:Genes, Viral; D005822:Genetic Vectors / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000276:immunology* / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D045402:Parainfluenza Virus 5 / Q000235:genetics* / Q000276:immunology; D019213:Rubulavirus / Q000235:genetics* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014709:Vero Cells
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines